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Endogenous opioids regulate moment-to-moment neuronal communication and excitability

Author

Listed:
  • Bryony L. Winters

    (Discipline of Pharmacology, School of Medical Sciences, University of Sydney)

  • Gabrielle C. Gregoriou

    (Discipline of Pharmacology, School of Medical Sciences, University of Sydney)

  • Sarah A. Kissiwaa

    (Discipline of Pharmacology, School of Medical Sciences, University of Sydney)

  • Oliver A. Wells

    (Discipline of Pharmacology, School of Medical Sciences, University of Sydney)

  • Danashi I. Medagoda

    (Discipline of Pharmacology, School of Medical Sciences, University of Sydney)

  • Sam M. Hermes

    (Oregon Health and Science University)

  • Neil T. Burford

    (Bristol-Myers Squibb)

  • Andrew Alt

    (Bristol-Myers Squibb)

  • Sue A. Aicher

    (Oregon Health and Science University)

  • Elena E. Bagley

    (Discipline of Pharmacology, School of Medical Sciences, University of Sydney)

Abstract

Fear and emotional learning are modulated by endogenous opioids but the cellular basis for this is unknown. The intercalated cells (ITCs) gate amygdala output and thus regulate the fear response. Here we find endogenous opioids are released by synaptic stimulation to act via two distinct mechanisms within the main ITC cluster. Endogenously released opioids inhibit glutamate release through the δ-opioid receptor (DOR), an effect potentiated by a DOR-positive allosteric modulator. Postsynaptically, the opioids activate a potassium conductance through the μ-opioid receptor (MOR), suggesting for the first time that endogenously released opioids directly regulate neuronal excitability. Ultrastructural localization of endogenous ligands support these functional findings. This study demonstrates a new role for endogenously released opioids as neuromodulators engaged by synaptic activity to regulate moment-to-moment neuronal communication and excitability. These distinct actions through MOR and DOR may underlie the opposing effect of these receptor systems on anxiety and fear.

Suggested Citation

  • Bryony L. Winters & Gabrielle C. Gregoriou & Sarah A. Kissiwaa & Oliver A. Wells & Danashi I. Medagoda & Sam M. Hermes & Neil T. Burford & Andrew Alt & Sue A. Aicher & Elena E. Bagley, 2017. "Endogenous opioids regulate moment-to-moment neuronal communication and excitability," Nature Communications, Nature, vol. 8(1), pages 1-15, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14611
    DOI: 10.1038/ncomms14611
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